Process for the preparation of a boron-substituted porphyrin

Abstract

Processes are disclosed for the preparation of a compound having the formula: (I) and intermediate compounds wherein M is a single-photon-emission tomography imageable radiometal and / or a paramagnetic metal, R is hydrogen or a halogen provided that at least one R is halogen and Y is selected from ortho, meta or para O(CH2)nC2HB9H10 or O(CH2)nC2HB10H10 wherein n is 0 or an integer from 1 to 20 and O(CH2)nC2HB9H10 is nido ortho-, meta- or para-carborane and O(CH2)nC2HB10H10 is ortho-, meta- or para-carborane.

Description

[0001]The present invention relates to a process for the production of a porphyrin of formula (I) and further to a process for the production of an intermediate compound such as compounds of formula (II).[0002]Radiotherapy, although widely used in the management and the treatment of early to advanced stage cancers, has many drawbacks including normal tissue damage and burdensome treatment schedules (up to 6 weeks). Clinical radiotherapy and chemotherapy deliver survival rates that remain inadequate and in some instances totally unacceptable. However, where there is no alternative treatment, which is the case for the vast majority of cancer patients, the use of radiotherapeutic modalities prevails. It is projected that current research efforts will improve the delivery and the outcome of radiotherapy by only 10% over the next 10 years. That is, an increase from 30% to 33% cure rate, with the remaining balance of treatment achieving 70% palliation. A major challenge is to significantl...

AI Technical Summary

Benefits of technology

The invention provides a process for preparing a compound of formula I, which involves combining a compound of formula Y with a compound of formula M to form a compound of formula IV. The compound of formula IV is then oxidized to form a compound of formula II. The compound of formula II is then combined with the acetate of the metal M to form a compound of formula III. The process allows for the one-pot synthesis of the compound of formula I, which is preferred. The invention also provides a process for producing a compound of formula II by combining an aldehyde with pyrrole in the presence of a Lewis acid catalyst, and oxidizing the resulting compound. The process is efficient and avoids the need for isolation and purification of intermediate compounds.

Problems solved by technology

Radiotherapy, although widely used in the management and the treatment of early to advanced stage cancers, has many drawbacks including normal tissue damage and burdensome treatment schedules (up to 6 weeks).

Clinical radiotherapy and chemotherapy deliver survival rates that remain inadequate and in some instances totally unacceptable.

However, where there is no alternative treatment, which is the case for the vast majority of cancer patients, the use of radiotherapeutic modalities prevails.

A major challenge is to significantly improve this cure rate without compromising normal tissue tolerance.

However, IMRT is data hungry and requires information on the exact dimensions of a tumour and its spread, and small movements of the tumour (0.1 mm-1 mm) that arise from breathing and the heart beat result in less than optimal x-ray dose delivery to guerrilla cells at the edges of the tumour.

Such cells escape treatment and can result in tumour recurrence.

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